Caffeine tests

Smith, B., Rafferty, J., Lindgren, K., Smith, D. and Nespor, A., Chronic and acute effects of caffeine Testing a biobehavorial model. Physiol Behav, 51, 131-137, 1991. 

Bertilsson, L. et al. (1994). Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test. Br. J. Clin. Pharmacol, 38,471-3. 

Tantcheva-Poor, I., Zaigler, M., Rietbrock, S. et al. (1999). Estimation of cytochrome P450 CYP1A2 activity in 863 healthy Caucasians using a saliva-based caffeine test. Pharmacogenetics, 9, 131—44. 

Bertilsson, L., Carrillo, J.A., Dahl, M.L., Llerena, A., Aim, C., Bondesson, U., Lindstrom, L., Rodriguez dela Rubia, I., Ramos, S. and Benitez, J. (1994) Clozapine disposition covaries with CYP1A2 activity determined hy a caffeine test. British Journal of Clinical Pharmacology, 38 (5), 471 173. 

Ozdemir V, Kalow W, Posner P, Collins EJ, Kennedy JL, Tang BK, Albers LJ, Reist C, Roy R, Walkes W, Afra P. CYP1A2 activity as measured by a caffeine test predicts clozapine and active metabolite steady-state concen-trationin patients with schizophrenia. J Clin Psychopharmacol 2001 21 398-407. 

Caffeine test subjects with a AFMU/1MX ratio <0.55 or a AFMU/(AFMU+1MX+1MU) ratio < 0.26 are slow acetylators (Fuchs 1999). Higher activity has been observed in black as compared to white subjects (Relling 1992), and a gender effect has generally not been observed (Kashuba 1998). 

The urinary caffeine test is not based on assays of specific substrates and products of NAT2 ( including other metabolism pathways involving at least xanthine-oxidases), and is affected by diet habits, xanthine-oxidase inhibitors such as allopurinol (Fuchs 1999), or other drugs (Klebovitch 1995). NAT activities are affected by anti-inflammatory drugs. Of note, acetominophen is an inhibitor of NAT2 in vivo (Rothen 1998). 

Grant DM, Tang BK, Kalow W (1984) A simple test for acetylator phenotype using caffeine test. Br J Clin Pharmacol 17 459 164... 

Klebovitch I, Rautio A, Salonpaa et al. (1995) Antipyrine, coumarin and glipizide affect N-acetylation measured by caffeine test. Biomedicine and Pharmacotherapy 49 225-227... 

Figure 43-12 Histogram of NAT2 phenotypical activities as obtained by the caffeine test 5 hr urine collection obtained after administration of caffeine, and analyzed for caffeine metabolite concentrations.Values represent the logarithmically transformed ratio of metabolites 5-acetylamino-6-formylamino-3-methy -uracil (AFMU) and I-methyixanthine (IX). From the distinct biomodal distribution an anti mode of log(0.50)...

In 21 healthy subjects, allopurinol 300 mg daily for 8 days altered the levels of urinary caffeine metabolites of a single 200-mg dose of caffeine. In particular, the metabolic ratio used to determine whether people are fast or slow acetylators was substantially changed. Thus, allopurinol may invalidate the results of phenotyping with the urinary caffeine test. In addition, the caffeine metabolite ratio used to express the activity of the cytochrome P450 isoenzyme CYP1A2 was not stable when allopurinol was used. This interaction is of relevance to research rather than clinical practice. 

The interaction between caffeine and mexiletine appears to be established, but its clinical importance is uncertain. Some of the adverse effects of mexiletine might be partially due to caffeine-retention (from drinking tea, coffee, cola drinks, etc.). In excess, caffeine can cause jitteriness, tremor and insomnia. It has also been suggested that the caffeine test for liver function might be impaired by mexiletine. Be alert for these possible effects. 

A large number of molecules have provided experimental evidence of neuroprotection in in vitro and in vivo models of Parkinson s disease and many of these putative neuroprotective substances are now the objects of clinical trials. Recently, a team of experts has identified potential neuroprotective agents to be tested in pilot studies [4]. Twelve compounds have been considered for clinical trials caffeine, coenzyme Q 10, creatine, estrogen, GPI1485, GM-1 ganglioside, minocycline, nicotine, pramipexole, ropinirol, rasagiline, and selegiline (for individual discussion see [4]). 

The caffeine contracture test involves exposing viable muscle fibers to incremental doses of caffeine from 0.5-32 mM, the concentration being increased every four min if no contraction develops. A positive caffeine contracture test is defined as the development of 0.2 g tension at 2 tiM caffeine, or > 7% tension change from baseline with 2 mM caffeine. 

In a joint halothane-caffeine contracture test, both caffeine and halothane are used. A positive test is defined as the development of 1 g contracture after exposure of viable muscle fibers to a concentration of 1 mM or less caffeine in the presence of 1% halothane. 

False negative muscle contraction tests are very rare. To date, a negative muscle contraction test rules out MH. A false negative test can be explained by the presence of two types of muscle fibers in a MH susceptible patient the response being dependent on the proportion of the two types of muscle fibers. The K-type designation is used to describe a patient who has a positive joint halothane-caffeine contracture, but a negative separate halothane or caffeine contracture. Whether K-type individuals are MH-susceptible or not is a controversial issue. 

Mackenzie, A.E., Allen, G., Lahey, D., Crossen, M.L., Nolan, K., Mettler, G., Worton, R.G., MacLen-nan, D.H., Korneluk, R. (1991). A comparison of the caffeine halothane muscle contracture test with the molecular genetic diagnosis of malignant hyperthermia. Anesthesiology 75,4-8. 

Methods of test for coffee and coffee products. Part 12. Coffee determination of caffeine content (routine method by HPLC), British Standards Institution, United Kingdom, British-Standard, BS 5752 Part 12, 1992. 

Collomp and associates,52 using a Wingate Anaerobic Test, found that caffeine did not affect maximal anaerobic capacity or power in six untrained subjects. Bond et al.29 found no differences in peak anaerobic... 

Finally, there is virtually no mention of the fact that the majority of test subjects in the caffeine research literature are reported to be males, so that hormonal differences in respect to caffeine s ergogenic effects may be a topic that requires further examination. 

Flinn et al.66 conducted an interesting study using nine recreational athletes who were caffeine naive. A 10 mg/kg dose was administered 3 h prior to testing on a cycle ergometer. These researchers attributed their positive results to (1) the use of caffeine naive subjects, (2) high doses of caffeine, (3) the timing of the dose, 3 h prior to exercise allowing FFA levels to peak, and (4) the use of recreational rather than elite athletes. 

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